This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Heninger, S.
Right arrow Articles by Lyons, C. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Heninger, S.
Right arrow Articles by Lyons, C. R.

 Previous Article  |  Next Article 

Infection and Immunity, November 2006, p. 6067-6074, Vol. 74, No. 11
0019-9567/06/$08.00+0     doi:10.1128/IAI.00719-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Toxin-Deficient Mutants of Bacillus anthracis Are Lethal in a Murine Model for Pulmonary Anthrax{triangledown}

Sara Heninger,1,{dagger} Melissa Drysdale,2,{dagger} Julie Lovchik,2 Julie Hutt,3 Mary F. Lipscomb,4 Theresa M. Koehler,5 and C. Rick Lyons1,2*

Department of Molecular Genetics and Microbiology, University of New Mexico Health Science Center, Albuquerque, New Mexico 87131,1 Department of Internal Medicine, University of New Mexico Health Science Center, Albuquerque, New Mexico 87131,2 Lovelace Respiratory Research Institute, Albuquerque, New Mexico 87131,3 Department of Pathology, University of New Mexico Health Science Center, Albuquerque, New Mexico 87131,4 Department of Microbiology and Molecular Genetics, The University of Texas Houston Health Science Center, Houston, Texas 770305

Received 4 May 2006/ Returned for modification 14 June 2006/ Accepted 8 August 2006

Bacillus anthracis, the etiologic agent of anthrax, produces at least three primary virulence factors: lethal toxin, edema toxin, and a capsule. The capsule is absolutely required for dissemination and lethality in a murine model of inhalation anthrax, yet the roles for the toxins during infection are ill-defined. We show in a murine model that when spores of specific toxin-null mutants are introduced into the lung, dissemination and lethality are comparable to those of the parent strain. Mutants lacking one or more of the structural genes for the toxin proteins, i.e., protective antigen, lethal factor, and edema factor, disseminated from the lung to the spleen at rates similar to that of the virulent parental strain. The 50% lethal dose (LD50) and mean time to death (MTD) of the mutants did not differ significantly from those of the parent. The LD50s or MTDs were also unaffected relative to those of the parent strain when mice were inoculated intravenously with vegetative cells. Nonetheless, histopathological examination of tissues revealed subtle but distinct differences in infections by the parent compared to some toxin mutants, suggesting that the host response is affected by toxin proteins synthesized during infection.

* Corresponding author. Mailing address: Department of Internal Medicine, BMSB G41, University of New Mexico Health Science Center, 1 University of New Mexico, Albuquerque, NM 87131. Phone (505) 272-4450. Fax: (505) 272-4160. E-mail: Clyons{at}salud.unm.edu.

{triangledown} Published ahead of print on 21 August 2006.

Editor: J. T. Barbieri

{dagger} These authors contributed equally to this work.

Infection and Immunity, November 2006, p. 6067-6074, Vol. 74, No. 11
0019-9567/06/$08.00+0     doi:10.1128/IAI.00719-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Wu, W., Mehta, H., Chakrabarty, K., Booth, J. L., Duggan, E. S., Patel, K. B., Ballard, J. D., Coggeshall, K. M., Metcalf, J. P. (2009). Resistance of Human Alveolar Macrophages to Bacillus anthracis Lethal Toxin. J. Immunol. 183: 5799-5806 [Abstract] [Full Text]  
  • Cote, C. K., Bozue, J., Twenhafel, N., Welkos, S. L. (2009). Effects of altering the germination potential of Bacillus anthracis spores by exogenous means in a mouse model. J Med Microbiol 58: 816-825 [Abstract] [Full Text]  
  • Skoble, J., Beaber, J. W., Gao, Y., Lovchik, J. A., Sower, L. E., Liu, W., Luckett, W., Peterson, J. W., Calendar, R., Portnoy, D. A., Lyons, C. R., Dubensky, T. W. Jr. (2009). Killed but Metabolically Active Bacillus anthracis Vaccines Induce Broad and Protective Immunity against Anthrax. Infect. Immun. 77: 1649-1663 [Abstract] [Full Text]  
  • Loving, C. L., Khurana, T., Osorio, M., Lee, G. M., Kelly, V. K., Stibitz, S., Merkel, T. J. (2009). Role of Anthrax Toxins in Dissemination, Disease Progression, and Induction of Protective Adaptive Immunity in the Mouse Aerosol Challenge Model. Infect. Immun. 77: 255-265 [Abstract] [Full Text]  
  • Chand, H. S., Drysdale, M., Lovchik, J., Koehler, T. M., Lipscomb, M. F., Lyons, C. R. (2009). Discriminating Virulence Mechanisms among Bacillus anthracis Strains by Using a Murine Subcutaneous Infection Model. Infect. Immun. 77: 429-435 [Abstract] [Full Text]  
  • Lisanby, M. W., Swiecki, M. K., Dizon, B. L. P., Pflughoeft, K. J., Koehler, T. M., Kearney, J. F. (2008). Cathelicidin Administration Protects Mice from Bacillus anthracis Spore Challenge. J. Immunol. 181: 4989-5000 [Abstract] [Full Text]  
  • Fink, S. L., Bergsbaken, T., Cookson, B. T. (2008). Anthrax lethal toxin and Salmonella elicit the common cell death pathway of caspase-1-dependent pyroptosis via distinct mechanisms. Proc. Natl. Acad. Sci. USA 105: 4312-4317 [Abstract] [Full Text]  
  • Sanz, P., Teel, L. D., Alem, F., Carvalho, H. M., Darnell, S. C., O'Brien, A. D. (2008). Detection of Bacillus anthracis Spore Germination In Vivo by Bioluminescence Imaging. Infect. Immun. 76: 1036-1047 [Abstract] [Full Text]  
  • Peterson, J. W., Comer, J. E., Baze, W. B., Noffsinger, D. M., Wenglikowski, A., Walberg, K. G., Hardcastle, J., Pawlik, J., Bush, K., Taormina, J., Moen, S., Thomas, J., Chatuev, B. M., Sower, L., Chopra, A. K., Stanberry, L. R., Sawada, R., Scholz, W. W., Sircar, J. (2007). Human Monoclonal Antibody AVP-21D9 to Protective Antigen Reduces Dissemination of the Bacillus anthracis Ames Strain from the Lungs in a Rabbit Model. Infect. Immun. 75: 3414-3424 [Abstract] [Full Text]  
  • Loving, C. L., Kennett, M., Lee, G. M., Grippe, V. K., Merkel, T. J. (2007). Murine Aerosol Challenge Model of Anthrax. Infect. Immun. 75: 2689-2698 [Abstract] [Full Text]  
  • Drysdale, M., Olson, G., Koehler, T. M., Lipscomb, M. F., Lyons, C. R. (2007). Murine Innate Immune Response to Virulent Toxigenic and Nontoxigenic Bacillus anthracis Strains. Infect. Immun. 75: 1757-1764 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»